GRIM-19 represses the proliferation and invasion of cutaneous squamous cell carcinoma cells associated with downregulation of STAT3 signaling

Abstract

The gene associated with retinoid-interferon-induced mortality-19 (GRIM-19) has been identified as a tumor suppressor in many human cancers. However, little is known about the role of GRIM-19 in cutaneous squamous cell carcinoma (CSCC). Here, we aimed to investigate the potential function of GRIM-19 in CSCC and explore the underlying molecular mechanisms. We found that GRIM-19 protein and transcript levels were significantly decreased in CSCC cell lines. Overexpression of GRIM-19 suppressed the proliferation and invasion of CSCC cells, whereas knockdown of GRIM-19 promoted the proliferation and invasion of CSCC cells. Also, we found that overexpression of GRIM-19 inhibited the phosphorylation and transcription activity of the signal transducer and activator of transcription 3 (STAT3). Overexpression of GRIM-19 also suppressed the expression of STAT3 target genes, including cyclin D1, Bcl-2 and metal matrix proteinase 2. By contrast, knockdown of GRIM-19 showed the opposite effect. Moreover, suppression of STAT3 significantly attenuated the effect of GRIM-19 knockdown on induction of proliferation, invasion, and STAT3 target genes in CSCC cells. Taken together, our data show that GRIM-19 suppresses the proliferation and invasion of CSCC cells associated with downregulation of STAT3 signaling, suggesting a tumor suppressive role of GRIM-19 in CSCC. Our study suggests that decreased expression of GRIM-19 may contribute to the development and progression of CSCC and that GRIM-19 may serve as a potential therapeutic target for CSCC treatment.

Keywords: Cutaneous squamous cell carcinoma; GRIM-19; STAT3.